Mitochondria-transferred macrophages promote Schwann cell-mediated myelin repair and erectile function recovery via the H3K27ac/FDFT1/cholesterol biosynthesis axis in CNI-ED

Cavernous nerve injury (CNI) is a leading cause of postoperative erectile dysfunction (ED), and effective etiological therapies are lacking. In this study, we constructed mitochondria-transferred macrophages (MTM) with an enhanced M2 reparative phenotype and metabolic activity to treat CNI-ED. In a rat model of bilateral CNI, MTM treatment significantly restored erectile function, preserved cavernous tissue structure, and promoted myelination and axonal regeneration of the injured cavernous nerve. Mechanistically, MTM transferred mitochondria to Schwann cells (SCs), elevated acetyl-CoA levels, increased H3K27ac enrichment at the FDFT1 promoter, and upregulated cholesterol biosynthesis. Inhibition of histone acetylation or cholesterol synthesis impaired SCs repair and erectile function recovery, whereas supplementation with the cholesterol precursor (squalene) reversed these effects. These findings identify a mitochondrial-epigenetic-lipid metabolic axis that drives SC-mediated myelin repair, providing a promising therapeutic strategy for CNI-ED and other demyelinating neurological disorders.